Trial Outcomes & Findings for A Study Comparing Two Forms of Tafamidis Without Food and the Amount of Tafamidis in the Blood With Food (NCT NCT05498701)
NCT ID: NCT05498701
Last Updated: 2024-06-03
Results Overview
AUCinf is defined as area under the concentration-time curve from time 0 to infinity, and calculated by AUC(0-tlast) + (Clast\*/kel), where Clast\* is the estimated plasma concentration at the last quantifiable time point (Clast) estimated form the log-linear regression analysis Clast\* = Clast x e\^(-kel x tlast)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
Predose and 0.5, 1,2,3,4,6,8,12,24 (Day 2),48 (Day 3),72 (Day 4),96 (Day 5),120 (Day 6),144 (Day 7), and 168 (Day 8) hours post dose
Results posted on
2024-06-03
Participant Flow
A total of 22 participants were enrolled in this study. Eleven participants were randomized to Sequence 1 and 11 participants were randomized to Sequence 2, all 22 participants received study interventions.
Participant milestones
| Measure |
Sequence 1
Participants randomized to Sequence 1 received tafamidis free acid tablet 12.2 mg, fasted (Test) in Period 1 followed by commercial tafamidis meglumine soft gelatin capsule 20 mg fasted (Reference) in Period 2 and tafamidis free acid tablet 12.2 mg, fed in Period 3. Each period was separated by a washout of at least 16 days between administration of study drug.
|
Sequence 2
Participants randomized to Sequence 2 received commercial tafamidis meglumine soft gelatin capsule 20 mg, fasted (Reference) in Period 1 followed by tafamidis free acid tablet 12.2 mg, fasted (Test) in Period 2 and tafamidis free acid tablet 12.2 mg, fed in Period 3. Each period was separated by a washout of at least 16 days between administration of study drug.
|
|---|---|---|
|
Period 1
STARTED
|
11
|
11
|
|
Period 1
COMPLETED
|
11
|
11
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
11
|
11
|
|
Period 2
COMPLETED
|
11
|
11
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
|
Period 3
STARTED
|
11
|
11
|
|
Period 3
COMPLETED
|
10
|
11
|
|
Period 3
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Participants randomized to Sequence 1 received tafamidis free acid tablet 12.2 mg, fasted (Test) in Period 1 followed by commercial tafamidis meglumine soft gelatin capsule 20 mg fasted (Reference) in Period 2 and tafamidis free acid tablet 12.2 mg, fed in Period 3. Each period was separated by a washout of at least 16 days between administration of study drug.
|
Sequence 2
Participants randomized to Sequence 2 received commercial tafamidis meglumine soft gelatin capsule 20 mg, fasted (Reference) in Period 1 followed by tafamidis free acid tablet 12.2 mg, fasted (Test) in Period 2 and tafamidis free acid tablet 12.2 mg, fed in Period 3. Each period was separated by a washout of at least 16 days between administration of study drug.
|
|---|---|---|
|
Period 3
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Study Comparing Two Forms of Tafamidis Without Food and the Amount of Tafamidis in the Blood With Food
Baseline characteristics by cohort
| Measure |
Sequence 1
n=11 Participants
Participants randomized to Sequence 1 received tafamidis free acid tablet 12.2 mg, fasted (Test) in Period 1 followed by commercial tafamidis meglumine soft gelatin capsule 20 mg fasted (Reference) in Period 2 and tafamidis free acid tablet 12.2 mg, fed in Period 3. Each period was separated by a washout of at least 16 days between administration of study drug.
|
Sequence 2
n=11 Participants
Participants randomized to Sequence 2 received commercial tafamidis meglumine soft gelatin capsule 20 mg, fasted (Reference) in Period 1 followed by tafamidis free acid tablet 12.2 mg, fasted (Test) in Period 2 and tafamidis free acid tablet 12.2 mg, fed in Period 3. Each period was separated by a washout of at least 16 days between administration of study drug.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.0 Years
n=5 Participants
|
37.0 Years
n=7 Participants
|
39.5 Years
n=5 Participants
|
|
Age, Customized
<18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
18-25 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Customized
26-35 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Customized
36-45 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Customized
>45 years
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1,2,3,4,6,8,12,24 (Day 2),48 (Day 3),72 (Day 4),96 (Day 5),120 (Day 6),144 (Day 7), and 168 (Day 8) hours post dosePopulation: All participants who received at least 1 dose of tafamidis and who had at least 1 of the PK parameters of interest calculated. Here "Number of Participants Analyzed" signifies participants who contributing to this outcome measure.
AUCinf is defined as area under the concentration-time curve from time 0 to infinity, and calculated by AUC(0-tlast) + (Clast\*/kel), where Clast\* is the estimated plasma concentration at the last quantifiable time point (Clast) estimated form the log-linear regression analysis Clast\* = Clast x e\^(-kel x tlast)
Outcome measures
| Measure |
Tafamidis Free Acid 12.2 mg Oral Tablet (Fasted)
n=16 Participants
Participants received a single tafamidis free acid tablet 12.2 mg under fasted condition orally on Day 1 of Period 1 for participants randomized in Sequence 1 and on Day 1 of Period 2 for participants randomized in Sequence 2.
|
Tafamidis Meglumine 20 mg Oral Capsule (Fasted)
n=18 Participants
Participants received a single commercial tafamidis meglumine capsule 20 mg orally under fasted condition on Day 1 of Period 2 for participants randomized in Sequence 1 and on Day 1 of Period 1 for participants randomized in Sequence 2.
|
Tafamidis Free Acid 12.2 mg Oral Tablet (Fed)
n=17 Participants
Participants received a single tafamidis free acid tablet 12.2 mg orally under fed condition on Day 1 of Period 3 for participants randomized in Sequence 1 and Sequence 2.
|
|---|---|---|---|
|
Pharmacokinetics(PK) Parameter - Area Under the Concentration-time Curve to Infinity (AUCinf) of PF-06291826
|
60670 Nanograms * hour per milliliter
Geometric Coefficient of Variation 24
|
67690 Nanograms * hour per milliliter
Geometric Coefficient of Variation 22
|
60210 Nanograms * hour per milliliter
Geometric Coefficient of Variation 28
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1,2,3,4,6,8,12,24 (Day 2),48 (Day 3),72 (Day 4),96 (Day 5),120 (Day 6),144 (Day 7), and 168 (Day 8) hours post dosePopulation: All participants who received at least 1 dose of tafamidis and who had at least 1 of the PK parameters of interest calculated. Here "Number of Participants Analyzed" signifies participants who contributing to this outcome measure.
Cmax is defined as maximum observed concentration.
Outcome measures
| Measure |
Tafamidis Free Acid 12.2 mg Oral Tablet (Fasted)
n=16 Participants
Participants received a single tafamidis free acid tablet 12.2 mg under fasted condition orally on Day 1 of Period 1 for participants randomized in Sequence 1 and on Day 1 of Period 2 for participants randomized in Sequence 2.
|
Tafamidis Meglumine 20 mg Oral Capsule (Fasted)
n=18 Participants
Participants received a single commercial tafamidis meglumine capsule 20 mg orally under fasted condition on Day 1 of Period 2 for participants randomized in Sequence 1 and on Day 1 of Period 1 for participants randomized in Sequence 2.
|
Tafamidis Free Acid 12.2 mg Oral Tablet (Fed)
n=17 Participants
Participants received a single tafamidis free acid tablet 12.2 mg orally under fed condition on Day 1 of Period 3 for participants randomized in Sequence 1 and Sequence 2.
|
|---|---|---|---|
|
PK Parameter - Maximum Observed Concentration (Cmax) of PF-06291826
|
1046 Nanograms per milliliter
Geometric Coefficient of Variation 19
|
1291 Nanograms per milliliter
Geometric Coefficient of Variation 21
|
891.2 Nanograms per milliliter
Geometric Coefficient of Variation 18
|
Adverse Events
Tafamidis Free Acid 12.2 mg Oral Tablet (Fasted)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Tafamidis Meglumine 20 mg Oral Capsule (Fasted)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Tafamidis Free Acid 12.2 mg Oral Tablet (Fed)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tafamidis Free Acid 12.2 mg Oral Tablet (Fasted)
n=22 participants at risk
Participants received a single tafamidis free acid tablet 12.2 mg under fasted condition orally on Day 1 of Period 1 for participants randomized in Sequence 1 and on Day 1 of Period 2 for participants randomized in Sequence 2.
|
Tafamidis Meglumine 20 mg Oral Capsule (Fasted)
n=22 participants at risk
Participants received a single commercial tafamidis meglumine capsule 20 mg orally under fasted condition on Day 1 of Period 2 for participants randomized in Sequence 1 and on Day 1 of Period 1 for participants randomized in Sequence 2.
|
Tafamidis Free Acid 12.2 mg Oral Tablet (Fed)
n=21 participants at risk
Participants received a single tafamidis free acid tablet 12.2 mg orally under fed condition on Day 1 of Period 3 for participants randomized in Sequence 1 and Sequence 2.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
18.2%
4/22 • The time period for collecting AEs for each participant begins from the time the participant provided informed consent up to 35 days after administration of the final dose of study intervention (approximately 11 weeks).
Same event may appear as both a NSAE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety set.
|
9.1%
2/22 • The time period for collecting AEs for each participant begins from the time the participant provided informed consent up to 35 days after administration of the final dose of study intervention (approximately 11 weeks).
Same event may appear as both a NSAE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety set.
|
19.0%
4/21 • The time period for collecting AEs for each participant begins from the time the participant provided informed consent up to 35 days after administration of the final dose of study intervention (approximately 11 weeks).
Same event may appear as both a NSAE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety set.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER